This invention relates to novel substituted .beta.-carbolines and pharmaceutical compositions comprising them, to a process for the preparation thereof, and to the use thereof as medicinal agents.
SUMMARY OF THE INVENTION
In a composition aspect, this invention relates to .beta.-carbolines of general Formula I: ##STR4## wherein R.sup.3 is a 5-oxadiazolyl group of the formula: ##STR5## wherein R' is C.sub.1-3 alkyl or C.sub.3-6 cycloalkyl and R" is C.sub.1-4 alkyl; R.sup.4 is hydrogen, methyl, ethyl or methoxymethyl; and R.sup.A is aryl of the formula ##STR6## or aralkyl of the formula ##STR7## wherein X is C.sub.1-12 straight-chain, branched-chain, saturated or unsaturated alkyl or a corresponding alkyl group with a CH.sub.2 -group substituted by a carbonyl group, and R"' is one or more of fluorine, chlorine, bromine, or iodine, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-5 acyloxy, phenyl, C.sub.2-5 alkylenedioxy, trifluoromethyl, nitrilo, nitro or --NR.sup.IV R.sup.V wherein R.sup.IV and R.sup.V, which can be the same or different, are hydrogen, C.sub.1-3 alkyl, C.sub.1-5 acyl or phenyl, or collectively with the amido nitrogen atom form a 3--to 6-membered hetero ring.
In a process aspect this invention relates to a process for the production of .beta.-carbolines of general Formula I wherein
(a) a substituted hydroxy-.beta.-carboline of general Formula II ##STR8## wherein R.sup.3 and R.sup.4 have the values given above is reacted in a conventional manner with an esterification reagent of the general formula R.sup.A Y, wherein Y is chlorine, bromine, iodine or tosyl, and R.sup.A has the values given above, and, if desired, the thus-obtained compound of Formula I wherein R" stands for methyl or ethyl is conventionally transesterified; or
(b) a substituted .beta.-carboline-3-carboxylic acid of general Formula III ##STR9## wherein R.sup.A and R.sup.4 have the values given above, is reacted in conventional manner with an amidoxime of the general formula R'--C(.dbd.NOH)NH.sub.2 wherein R' has the values given above, to the corresponding 5-oxadiazolyl derivative.
In a further composition aspect, this invention relates to pharmaceutical compositions comprising a compound of general Formula I in admixture with a pharmaceutically acceptable carrier.
In a method-of-use aspect, this invention relates to the use of compounds of general Formula I as psycho-pharmaceuticals.